The exposure of phosphatidylserine (PS) and other aminophospholipids (aminoPL) on the surface of activated or injured blood cells and endothelium is thought to play a key role in the initiation and regulation of blood coagulation. De novo surface exposure of aminophospholipids has also been implicated in the activation of both complement and coagulation systems after tissue injury, and in removal of injured or apoptotic cells by the reticuloendothelial system. Although migration of these phospholipids (PL)from inner-to-outer plasma membrane leaflets is known to be triggered by elevated intracellular [Ca.sup.2+ ] ([Ca.sup.2+ ].sub.c) and to be associated with vesicular blebbing of the cell surface, little is known about the cellular constituents that participate in this process.
As described in Ser. No. 08/790,186, cell surface PS has a role in coagulation, programmed cell death and clearance by the reticuloendothelial system. Ser. No. 08/790,186 also describes regulation of the transmembrane distribution of PS, the role of calcium in the collapse of phospholipid asymmetry, and the role PL translocation in Scott Syndrome.
Basse, et al. and Stout, et al. recently reported the purification and preliminary characterization of an integral RBC membrane protein that, when reconstituted in liposomes, mediates a Ca.sup.2+ -dependent transbilayer movement of PL mimicking plasma membrane PL reorganization evoked upon elevation of [Ca.sup.2+ ].sub.c (F. Basse, et al., J. Biol. Chem. 271:17205-17210, 1996; J. G. Stout, et al., J. Clin. Invest. 99:2232-2238, 1997). Evidence that a protein of similar function must also be present in platelets was recently reported by Comfurius, et al. (P. Comfurius, et al., Biochemistry 35:7631-7634, 1996).
Needed in the art is a method for modulating the activity of phospholipid scramblase within a cell, organ or tissue in which one wishes either to reduce the potential for thrombosis, clot formation, or cell clearance (by decreasing cellular PL scramblase expression or activity) or to promote hemostasis or cell clearance (by increasing cellular PL scramblase expression or activity).